Prostaglandins are a group of closely related carboxylic acids containing a cyclopentane ring with two adjacent carbon side chains, one of which bears the carboxyl group at the terminal position. Most of the naturally occurring prostaglandins may be regarded as derivatives of the parent structure prostenoic acid. Natural prostaglandins are divided into four groups and although these may be named in accordance with their relationship to prostenoic acid, they are more conveniently referred to by the letters A, B, E, and F (shown below): all four groups have in common a trans.dbd.13,14 position bond, and a hydroxyl group at C.sub.15. ##STR1## Further, the E- and F-type possess an additional hydroxyl at C.sub.11, with the E-type bearing a carbonyl function at C.sub.9 while the F-type bears an hydroxyl at C.sub.9.
Prostaglandins of the E-type and their esters are extremely potent in causing various biological responses and, for this reason, are useful for pharmacological purposes. Among these purposes are use as hypotensives, antilipodemics, bronchodilators, fertility control agents, and gastric secretion inhibitors. Bergstrom, et al., Pharmacol. Rev. (20), 1, 1968, and the references cited therein. See also, U.S. Pat. Nos. 3,069,322 and 3,598,858 concerning esters of prostaglandins of the E-type. The basic problem in the pharmacological utilization of these drugs occurs in the relatively unstable nature of prostanglandin-like compounds of the E-type in conventional pharmaceutical formulations. These compounds tend to decompose, at and above room temperature, and in the presence of small amounts of acid or base. For example, PGE.sub.2 changes to PGA.sub.2 in the presence of acid, while PGE.sub.2 changes to PGB.sub.2 in the presence of base. Similarly, other prostaglandin-like compounds of the E-type change to their corresponding compounds of the A- and B-type. In general, it can be said that the E-type prostaglandins may be distinguished from A- and B-type prostaglandins by the presence of a hydroxyl at C.sub.11 (shown below), and the A and B types may be regarded as dehydration products of E-type compounds resulting from a removal of the C.sub.11 hydroxyl and the formation of a double bond in the ring. ##STR2## Even in neutral aqueous solution or in a neat state there is a gradual change for E-types to A-types and B-types. Stability of the E-types has been observed in some solutions and in solid form at -20.degree. C. or lower but storage at this temperature is impractical and administration to mammals practically impossible. Better success at stabilizations have been obtained with other solutions and compositions as described in U.S. Pat. Nos. 3,749,800; 3,826,823; 3,829,579 and 3,851,052 and by Srivastava et al., Lipids, (8), 592 (1973), wherein ethyl acetate, chloroform, and ethanol are used as solvents for prostaglandins of the E-types. Such solvents, however, are unsuitable for pharmaceutical dosage forms without dilution with water which causes rapid decomposition. A quantization of such decomposition may be found in Table I. The essence of the present invention resides in the discovery that prostaglandins and prostaglandin-like compounds of the E-type can be dissolved in the normally liquid substance known as triethyl citrate to provide an unexpectedly stable and useful pharmaceutical dosage form for the direct administration to warm-blooded animals. Prostaglandin stabilized by triethyl citrate of the present invention is particularly adaptable for oral administration of therapeutic doses of prostaglandins.